In a time-of-flight mass spectrometer, ions are accelerated by electric fields out of an extraction region into a field free flight tube which is terminated by an ion detector. By applying a pulsed electric field or by momentary ionization in constant electric fields, a group of ions or packet starts to move at the same instant in time, which is the start time for the measurement of the flight time distribution of the ions. The flight time through the apparatus is related to the mass to charge ratios of the ions. Therefore, the measurement of the flight time is equivalent to a determination of the ion's m/z value. (See, e.g., the Wiley and McLaren; and, the Laiko and Dodonov references cited below).
Only those ions present in the extraction zone of the ion accelerator, (also referred to as "the pulser"), in the instant when the starting pulse is applied are sent towards the detector and can be used for analysis. In fact, special care must be taken not to allow any ions to enter the drift section at any other time, as those ions would degrade the measurement of the initial ion package.
For this reason, the coupling of a continuously operating ion source to a time-of-flight mass spectrometer suffers from the inefficient use of the ions created in the ion source for the actual analysis in the mass spectrometer. High repetition rates of the flight time measurements and the extraction of ions from a large volume can improve the situation, but the effective duty cycles achieved varies as a function of mass and can be less then 10% at low mass.
If extremely high sensitivity mass analysis is required or if the number of ions created in the ion source is relatively small, there is need to make use of all the ions available. This requires some sort of ion storage in-between the analysis cycles. Time-of-flight instruments that use dc plate electrode configurations or three dimensional quadrupole ion traps for ion storage have been built and operated successfully. (See e.g., the Grix, Boyle, Mordehai, and Chien references cited below). While the storage efficiency of dc configurations is limited, with three dimensional quadrupole ion traps a compromise between efficient collisional trapping and collision free ion extraction has to be found.
In one embodiment of the present invention, a multiple pumping stage linear two dimensional multipole ion guide is configured in combination with a time-of-flight mass spectrometer with any type of ionization source to increase duty cycle and thus sensitivity and provide the capability to achieve mass to charge selection. Previous systems, such as the three dimensional ion trap/time-of-flight system of Lubman (cited below), have combined a storage system with time-of-flight, however, these systems' trapping time are long, on the order of a second, thus not taking full advantage of the speed at which spectra can be acquired and thereby limiting the intensity of the incoming ion beam. In addition, the three dimensional ion trap is strictly used as the acceleration region and storage region. Also, 100% duty cycle is not possible with the three dimensional ion trap TOF system due to the fact that the three dimensional ion trap can not be filled and emptied at the same time; in addition, there are currently electronic limitations with the operation of three dimensional ion traps (See e.g., Mordehai, cited below). In the embodiment of the invention described herein, it is possible to fill and release ions simultaneously from a two dimensional ion trap configured in a Time-Of-Flight mass analyzer resulting in improved duty cycle and hence sensitivity.
The use of a two dimensional multipole ion guide to store ions prior to mass analysis has been implemented by Dolnikowski et al. on a triple quadrupole mass spectrometer. A more recent combination was made by Douglas (U.S. Pat. No. 5,179,278) who combined a two dimensional multipole ion guide with a quadrupole ion trap mass spectrometer where all ions trapped in the multipole ion guide were emptied into the three dimensional ion trap prior to each time-of-flight pulse. Both of these systems are quite different from the current embodiment. In both of the above systems, the residence times of the ions in the linear two dimensional quadrupole ion guide were over 1-3 seconds, whereas, in the current embodiment the ions can be stored and pulsed out of the linear two dimensional multipole ion guide at a rate of more than 10,000/sec, thus utilizing much faster repetition rates. Due to the inherent fast mass spectral analysis feature of the time-of-flight mass analyzers, continuously generated incoming ions are analyzed at a much better overall transmission efficiency than the dispersive spectrometers such as quadrupoles, ion traps, sectors or Fourier Transform mass analyzers. When an ion storage device is coupled in front of a dispersive mass analyzer instrument, the overall transmission efficiency of an instrument, no doubt, increases; however, since the ion fill rate into the storage device is much faster than the full spectral mass analysis rate, the overall transmission efficiencies are limited by the mass spectral scan rates of the dispersive instruments which are at best on the order of seconds. Time-of-flight mass analyzers, on the other hand, can make full use of the fast fill rates of the incoming continuous stream of ions since the full mass spectral time-of-flight pulse rates of 10,000 per second and more can well exceed the fill rates into a storage device. One aspect of the invention is that only a portion of the ions stored in the two dimensional ion trap are released into the time-of-flight region for each time-of-flight pulse, allowing an increase in duty cycle and sensitivity when compared with non trapping time-of-flight operation.
Also unique to this embodiment is the fact that the ion packet pulse out of the linear two dimensional multipole ion guide forms a low resolution time of flight separation of the different m/z ions into the pulser where the timing is critical between when the pulse of ions are released from the linear two dimensional multipole ion guide and the time at which the pulser is activated. This is to say that the linear two dimensional multipole ion guide pulse time and the delay time to raise the pulser can be controlled to achieve 100% duty cycle on any ion in the mass range or likewise a 0% duty cycle on any ion in the mass range or any duty cycle in between. Also, as pointed out by Douglas (U.S. Pat. No. 5,179,278), an ion guide can hold many more ions than what the ion trap mass analyzer can use. This decreases the duty cycle of the system if all trapped ions are released together to be mass analyzed. In contrast, that is not an issue in the current embodiment as only a portion of the trapped ions are mass analyzed per time-of-flight pulse.
As the linear two dimensional multipole ion guide trap is filled with more ions, the space charging effects or coulombic interactions between the ions increase resulting in two major consequences. First, the mass spectral characteristics may change due to overfilling of the storage device where more fragmentation will occur due to strong ionic interactions. Second, the internal energy of the ions will increase, making it harder to control and stop the ions going into a mass analyzer device. The above problems can again be overcome using a time-of-flight mass analyzer at fast scan rates which will not allow excessive charge build up in the storage ion guide. Operating at very fast acquisition rates, the time-of-flight instrument does require intricate timing of the trapping and the pulsing components.